Bay Area Breast Cancer SPORE investigators pursue translational research on development of novel, molecularly targeted therapeutic agents and on identification of molecular markers that predict disease recurrence or response to therapy. All projects are based on and contribute to our knowledge of the basic genetic and biological events that enable cancer genesis and progression. The suite of therapeutic and marker studies now under study address all aspects of breast cancer progression. This research is carried out in five Projects and four Cores. New ideas and investigators are bought into the SPORE through Developmental Project and Career Development awards. Project 1 is developing immunoliposomes for targeted delivery of a suite of therapeutic agents. Project 2 focuses on identification of markers that improve prediction of response to RTK pathway inhibitors. Project 3 is exploiting a new in vitro model of early cancer development to identify markers of risk and targets for chemoprevention. Project 4 is developing therapeutic agents that inhibit proliferation and induce apoptosis by forcing telomerase misfunction. Project 5 is a population-based effort to identify predictors of recurrence in women with DCIS. Core 1 provides administration and organizational support for all SPORE investigators. Core 2 collects and manages tissue resources and outcomes information on breast cancer patients for SPORE investigators. Core 3 supports preclinical evaluations of novel therapeutic agents in xenograft models. Core 4 supports the involvement of breast cancer advocates in SPORE research. Two current Development Projects are (a) exploring the utility of ductal lavage and nipple aspiration in identification of women at increased risk of developing breast cancer and (b) developing therapeutic antibodies to treat ERBB2 negative tumors. Two current Career Development awardees are (a) exploring the role of matrix metalloproteinase polymorphisms in cancer susceptibility and (b) developing an approach to breast cancer treatment using inhibitors of integrin signaling. The SPORE is located organizationally in the Cancer Center Breast Oncology Program and takes full advantage of 13 Cancer Center Cores.